This phase I trial studies the side effects and best dose of sorafenib tosylate when given together with riluzole in treating patients with solid tumors or melanoma that has spread to other places in the body and usually cannot be cured or controlled with treatment. Riluzole may stop or slow the growth of tumor cells. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving riluzole together with sorafenib tosylate may kill more tumor cells.

Maximum-tolerated dose of sorafenib tosylate and riluzole in patients with all types of solid tumors [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

Maximum tolerated dose is defined as the first dose level at which exactly 2/6 patients experience dose limiting toxicity (DLT), or at which 1/6 experience DLT and (due to de-escalation) at least 2/3 or 3/6 patients treated with the next higher dose level had DLT.

Secondary Outcome Measures:

Change in BCL-2 expression [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]

Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.

Change in BIM expression [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]

Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.

Change in MCL-1 expression [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]

Appropriate parametric (such as paired t-test) or nonparametric (such as Wilcoxon signed rank test) methods will be used.

Change in microvesicle quantification [ Time Frame: Baseline to 3 years ] [ Designated as safety issue: No ]

Pharmacokinetic parameters of the combination of riluzole with sorafenib tosylate [ Time Frame: On days 2, 8, 10, and 15 of each course ] [ Designated as safety issue: No ]

Suppression of MAPK and PI3K/AKT pathways [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Patients receive riluzole PO BID and sorafenib tosylate PO QD or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis

Correlative studies

Other: Pharmacological Study

Correlative studies

Drug: Riluzole

Given PO

Other Name: Rilutek

Drug: Sorafenib Tosylate

Given PO

Other Names:

BAY 43-9006 Tosylate

BAY 54-9085

Nexavar

sorafenib

Detailed Description:

PRIMARY OBJECTIVES:

I. To define a safe dose of sorafenib (sorafenib tosylate) to combine with riluzole in the treatment of patients with all types of solid tumors refractory to standard therapy or for whom no standard therapy exists.

SECONDARY OBJECTIVES:

I. To examine the correlation of clinical or radiologic response with signaling through the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways.

Patients receive riluzole orally (PO) twice daily (BID) and sorafenib tosylate PO once daily (QD) or BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for approximately 2-3 years.

Eligibility

Ages Eligible for Study:

18 Years and older (Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients must have histologically proven solid tumors (Phase I) with biopsiable tumor (expansion cohort) refractory to standard therapy or for whom no standard therapy exists or who decline standard therapy

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Patients must be willing and able to sign informed consent

Unlimited prior therapies are permitted for patients enrolled in the dose escalation phase of the study; patients in the expansion cohort of the study may not have any prior therapy with riluzole or sorafenib and must have biopsiable tumor

Patients with brain lesions that have been treated with whole brain radiotherapy and are clinically stable for at least 4 weeks, are not taking steroids and are not receiving enzyme-inducing anticonvulsants will be eligible

Exclusion Criteria:

Serious concomitant systemic disorders (including active infections) that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator

For patients who have received gamma knife or stereotactic radiosurgery, a 2 week washout is required; patients who have had other types of radiotherapy, chemotherapy or biologic agents within 3 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 3 weeks earlier to =< grade 1; at least 4 weeks must have elapsed since any major surgery; patients with prostate cancer may continue to receive hormonal therapy

History of allergic reactions attributed to riluzole or sorafenib

Women of child-bearing potential and men must agree to use adequate contraception (hormonal, barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for 2 weeks after discontinuation of riluzole and/or sorafenib; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; pregnant (positive pregnancy test) or lactating patients cannot participate

Known human immunodeficiency virus (HIV) infection or known history of active hepatitis B or C infection

Current, recent (within 4 weeks of the first treatment of this study), or planned participation in an experimental drug study (prevention trials are permitted if the trial is not testing a novel experimental agent)

Cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months

Any other hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug

Evidence or history of bleeding diathesis or coagulopathy

Major surgery or significant traumatic injury within 4 weeks of first study drug

The eligibility of patients taking medications that are potent modulators of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), cytochrome P450, family 2, subfamily B, polypeptide 6 (CYP2B6), subfamily 2, polypeptide 8 (2C8) will be determined following a review of their case by the principal investigator; every effort should be made to switch patients taking such agents or substances to other medications

Any condition that impairs the patient's ability to swallow whole pills

Any malabsorption problem

Anticipation of need for major surgical procedure during the course of the study

History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to day 1 of treatment

Serious, non-healing wound, ulcer, or bone fracture

Inability to comply with study and/or follow-up procedures

Anticoagulation with Lovenox (enoxaparin) is permitted, however, patients on anticoagulation with warfarin are not permitted on this study

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01303341